Present invention disclosed three-dimensional crystal structure of N-terminus polypeptide of influenza virus polymerase subunit (PA_N). PA_N is residues 1∼50 to 150-300 of influenza virus polymerase subunit PA. In three-dimensional structure, at least 40% of atoms showed same atomic coordinates, compared to that listed in Table. In other words, in three-dimensional structure of influenza virus polymerase subunit PA_N, 40% of atomic coordinates on carbon skeleton of residues of influenza virus polymerase subunit PA_N, showed less than or equal to 1.7Å of average variance, compared to the atomic coordinates listed in Table1. Present invention also disclosed the expression, purification, crystallization methods, and three-dimensional crystal structure of 256 residues in the N-terminus of influenza virus polymerase subunit PA, and applications of the crystal structure on drug screening and designing.